Mini-Abstract: Modified mRNA is an attractive and novel in vivo gene delivery method that allows high gene expression in variety of organs, including the heart. Expression is seen within 20 minutes following delivery and can last from several days and up to a week. The strength of Modified mRNA as a gene delivery therapy is in its safety, transiently, and high expressivity. It does not require nuclear localization or transcription and its integration into the genome is negligible. Most important, the modifications made to the mRNA allows it to avoid the innate immune system, specifically TLR activation, and reduce mRNA cleavage due to its lack of recognition by RNase. Our main goal is to unravel regenerative genes that can enhance cardiac regeneration after injury. For that, we are using modified mRNA as a novel gene delivery system to locally up-regulate or downregulate selected genes after myocardial infarction in small and large animal models.
Our goal: The Zangi lab’s goal is to induce cardiac regeneration after myocardial infraction using a gene therapy approach with modified mRNA. To achieve this, we plan to change the non-regenerative gene expression profile of adult cardiac muscle to grant regenerative capacity to adult heart after injury. Our plan is to investigate specific genes or signaling networks on both cellular (cell specific) and tissue (whole muscle) levels, using modified mRNA and other gene delivery approaches.
Publications:
Lipid Nanoparticles for Organ-Specific mRNA Therapeutic Delivery
Direct Reprogramming Induces Vascular Regeneration Post Muscle Ischemic Injury
Modified mRNA as a Therapeutic Tool for the Heart
Delivery of Modified mRNA in a Myocardial Infarction Mouse Model
Pkm2 Regulates Cardiomyocyte Cell Cycle and Promotes Cardiac Regeneration
Optimizing Modified mRNA In Vitro Synthesis Protocol for Heart Gene Therapy